Sinko P J, Amidon G L
College of Pharmacy, The University of Michigan, Ann Arbor 48109-1065.
Int J Pharm. 1992 Sep 20;85(1-3):181-7. doi: 10.1016/0378-5173(92)90147-t.
The absorption mechanism of several penicillins was characterized using in situ single-pass intestinal perfusion in the rat. The intrinsic membrane parameters were determined using a modified boundary layer model (fitted value +/- S.E.): Jmax* = 11.78 +/- 1.88 mM, Km = 15.80 +/- 2.92 mM, Pm* = 0, Pc* = 0.75 +/- 0.04 for ampicillin; Jmax* = 0.044 +/- 0.018 mM, Km = 0.058 +/- 0.026 mM, Pm* = 0.558 +/- 0.051, Pc* = 0.757 +/- 0.088 for amoxicillin; and Jmax* = 16.30 +/- 3.40 mM, Km = 14.00 +/- 3.30 mM, Pm* = 0, Pc* = 1.14 +/- 0.05 for cyclacillin. All of the aminopenicillins studied demonstrated saturable absorption kinetics as indicated by their concentration-dependent wall permeabilities. Inhibition studies were performed to confirm the existence of a nonpassive absorption mechanism. The intrinsic wall permeability (Pw*) of 0.01 mM ampicillin was significantly lowered by 1 mM amoxicillin and the Pw* of 0.01 mM amoxicillin was reduced by 2 mM cephradine consistent with competitive inhibition.
利用大鼠原位单通道肠道灌注法对几种青霉素的吸收机制进行了表征。使用改良的边界层模型确定固有膜参数（拟合值±标准误）：氨苄西林的Jmax* = 11.78 ± 1.88 mM，Km = 15.80 ± 2.92 mM，Pm* = 0，Pc* = 0.75 ± 0.04；阿莫西林的Jmax* = 0.044 ± 0.018 mM，Km = 0.058 ± 0.026 mM，Pm* = 0.558 ± 0.051，Pc* = 0.757 ± 0.088；环己西林的Jmax* = 16.30 ± 3.40 mM，Km = 14.00 ± 3.30 mM，Pm* = 0，Pc* = 1.14 ± 0.05。所有研究的氨基青霉素均表现出饱和吸收动力学，这由其浓度依赖性的肠壁通透性表明。进行抑制研究以证实非被动吸收机制的存在。1 mM阿莫西林可使0.01 mM氨苄西林的固有肠壁通透性（Pw*）显著降低，2 mM头孢拉定可使0.01 mM阿莫西林的Pw*降低，这与竞争性抑制一致。
